Nebulizer that is activated by negative inspiratory pressure

ABSTRACT

A nebulizer includes a body, an air channel section and medication reservoir. An air line extends through the air channel section. A venturi nozzle is configured to form at its end a low pressure mixing chamber. A primary suction line extends from the medication reservoir to the low pressure mixing chamber through which medication is drawn upward into the low pressure mixing chamber and mixed with air from the venturi nozzle and nebulized for discharge through a nebulizer outlet. The venturi nozzle, low pressure mixing chamber and air channel section are configured such that at standard temperature and pressure (STP) a differential pressure results in no medication that is drawn upward through the primary suction line for nebulization and discharged the through the nebulizer outlet until a negative inspiratory pressure is created from inhalation by a user.

PRIORITY APPLICATION(S)

This is a continuation application of Ser. No. 13/353,611 filed Jan. 19,2012, which claims priority to U.S. provisional application Ser. No.61/434,613, filed Jan. 20, 2011, the disclosures which are herebyincorporated herein by reference in their entirety.

RELATED APPLICATION(S)

This application is related to commonly assigned U.S. patent applicationSer. No. 11/431,689, now issued as U.S. Pat. No. 7,712,466; U.S. patentapplication Ser. No. 11/557,993, now issued as U.S. Pat. No. 7,726,306;U.S. patent application Ser. No. 11/611,425, filed Dec. 16, 2006, andU.S. patent application Ser. No. 12/724,785, filed Mar. 16, 2010, nowissued as U.S. Pat. No. 8,109,266.

FIELD OF THE INVENTION

The present invention relates to the field of nebulizers, and moreparticularly, this invention relates to nebulizers having a venturi. Thepresent invention also relates to the field of nebulizers configured forpediatric use and nebulizers having a flow meter function.

BACKGROUND OF THE INVENTION

Inhalation is a very old method of drug delivery. In the twentiethcentury it became a mainstay of respiratory care and was known asaerosol therapy. Use of inhaled epinephrine for relief of asthma wasreported as early as 1929, in England. Dry powder inhalers have beenused to administer penicillin dust to treat respiratory infections. In1956, the first metered dosed inhaler was approved for clinical use.

The scientific basis for aerosol therapy developed relatively late,following the 1974 Sugar Loaf conference on the scientific basis ofrespiratory therapy. A more complete history of the development ofaerosol therapy and the modern nebulizer is described in the 2004Phillip Kitridge Memorial Lecture entitled, “The Inhalation of Drugs:Advantages and Problems by Joseph L. Row; printed in the March 2005issue of Respiratory Care, vol. 50, no. 3.

Table 8 of the Respiratory Care article, referred to above, page 381,lists the characteristics of an ideal aerosol inhaler as follows:

TABLE 8 Dose reliability and reproducibility High lung-depositionefficiency (target lung deposition of 100% of nominal dose) Productionof the fine particles ≦ 5 μm diameter, with correspondingly low massmedian diameter Simple to use and handle Short treatment time Small sizeand easy to carry Multiple-dose capability Resistance to bacterialcontamination Durable Cost-effective No drug released to ambient-airEfficient (small particle size, high lung deposition) for the specificdrug being aerosolized Liked by patients and health care personnel

Standard nebulizers typically fail to achieve a number of thesecharacteristics because they waste medication during exhalation.Further, the particle size is often too large to reach the bottom of thelungs where the medication may be most needed. There is difficulty inestimating the dose of the drug being given to a patient and there isdifficulty in reproducing that dose. There is a possibility ofcontamination when opening the initially sterile kit, pouring medicationinto the cup, and assembling the pieces for use by a patient. There isalso considerable inefficiency in the medication delivery, with much ofit being deposited in the throat, rather than in the lungs.

Commonly assigned U.S. patent application Ser. No. 12/724,785 filed Mar.16, 2010, and published as 2010/0204602, the disclosure which is herebyincorporated by reference in its entirety, discloses a nebulizer havinga flow meter function that is applied to venturi type intra-oralnebulizers as disclosed in commonly assigned U.S. Pat. Nos. 7,712,466and 7,726,306 and U.S. patent application Ser. No. 11/611,425 andpublished as U.S. Patent Publication No. 2007/013764B, the disclosureswhich are hereby incorporated by reference in their entirety. Thesenebulizers are horizontally configured and include a venturi at arainfall chamber in one example, and in another example uses a valvingsystem. It would be advantageous if a more enhanced nebulizer could beprovided, for example, as the horizontal type nebulizer and venturi thatcould be breath activated and applicable for use as a pediatricnebulizer. It would also be advantageous if an enhanced flow meterfunction could be provided.

When a patient performs a treatment with the nebulizer, it would beadvantageous to determine if the patient's respiratory function hasimproved due to the use of the drug being administered. Also, it wouldbe advantageous for the patient to use the nebulizer for respiratoryexercise and incentive spirometry uses in which flow and pressure can bemeasured over time and pulmonary function testing performed.

SUMMARY OF THE INVENTION

In accordance with non-limiting examples, a nebulizer includes a bodyhaving an air channel section, a medication reservoir and a nebulizeroutlet configured to be received within an oral cavity of a patient. Anair line extends into the air channel section and has a venturi nozzleconfigured with the air channel section to form at the end of theventuri nozzle a low pressure mixing chamber. A primary suction lineextends from the medication reservoir to the low pressure mixing chamberthrough which medication is drawn upward into the low pressure mixingchamber and mixed with air from the venturi nozzle and nebulized fordischarge through the nebulizer outlet. The venturi nozzle, low pressuremixing chamber and air channel section are configured such that atstandard temperature and pressure (STP), a differential pressure resultsin no medication being drawn upward through the primary suction line fornebulization and being discharged through the nebulizer outlet, until anegative inspiratory pressure is created from inhalation by a user.

The air line, venturi nozzle and nebulizer outlet are horizontallyoriented when in use, in one example. Nebulization begins at a negativeinspiratory pressure of from about −3 cmH₂O to about −52 cmH₂O, in yetanother example. The venturi nozzle is positioned at a location to beplaced within a patient's oral cavity when the nebulizer is in use. Arainfall chamber is formed in the body into which the venturi nozzle andlow pressure mixing chamber are positioned. The nebulized medication andair exiting the venturi nozzle impacts a diffuser to aid nebulization.

A secondary suction line is formed within the rainfall chamber and drawsnebulized medication that drops down before discharge through thenebulizer outlet. In another example, an air flow sensor is positionedwithin the air channel section and configured to generate signalsindicative of air flow generated by a patient's involuntary cough eventoccurring at nebulization. A processor is interfaced with the air flowsensor and configured to receive the signals and evaluate theinvoluntary cough event.

In another example the nebulizer outlet is configured as an infantpacifier or lollipop. A housing encloses the body and has an endadjacent the nebulizer outlet and configured as an infant pacifier.

BRIEF DESCRIPTION OF THE DRAWINGS

Other objects, features and advantages of the present invention willbecome apparent from the detailed description of the invention whichfollows, when considered in light of the accompanying drawings in which:

FIG. 1 is cross-sectional view of a nebulizer in accordance with anon-limiting example that is activated by negative inspiratory pressureand can be configured as a pediatric nebulizer in one non-limitingexample and include in one embodiment a flow meter function.

FIGS. 2-3 are sectional views of the nebulizer shown in FIG. 1 andshowing a flow diagram of the airflow at 2 L/min at standard temperatureand pressure (STP).

FIGS. 4-5 are flow diagrams showing the airflow through the nebulizer ofFIG. 1 at 2 L/min at −3 cmH₂O.

FIGS. 6-7 are flow diagrams showing the airflow through the nebulizer ofFIG. 1 with 2 L/min at −15 cmH₂O.

FIGS. 8-9 are flow diagrams showing the airflow through the nebulizer ofFIG. 1 with 2 L/min at −52 cmH₂O.

FIG. 10 is a diagram showing the pressure gradient in the nebulizer ofFIG. 1 at standard temperature and pressure.

FIG. 11 is a diagram of the nebulizer of FIG. 1 showing the pressuregradient at −3 cmH₂O.

FIG. 12 is a sectional view of the nebulizer of FIG. 1 showing thepressure gradient at −15 cmH₂O.

FIG. 13 is a sectional view of the nebulizer of FIG. 1 showing thepressure gradient at −52 cmH₂O.

FIG. 14 is a sectional view of the nebulizer of FIG. 1 showing themedication flow upward at 2 L/min −3 cmH₂O.

FIG. 15 is a sectional view of the nebulizer of FIG. 1 showing themedication flow upward at 2 L/min −15 cmH₂O.

FIG. 16 is a sectional view of the nebulizer of FIG. 1 showing themedication flow upward at 2 L/min −52 cmH₂O.

FIG. 17 is a table showing respiratory pressures for the measured andpredicted MIP and MEP for males and females.

FIG. 18 is a general environmental view of a child sucking on apediatric nebulizer such as disclosed in FIGS. 19-22 in accordance withnon-limiting examples.

FIG. 19 is a general environmental view of a pediatric nebulizer used bythe infant shown in FIG. 18 in accordance with non-limiting examples.

FIG. 20 is a side sectional view in isometric of the pediatric nebulizershown in FIG. 19 that engages the patient's mouth.

FIG. 20A is a more detailed view of the pediatric nebulizer body withthe rainfall chamber, which includes an airflow sensor in accordancewith non-limiting examples.

FIG. 21 is another side sectional view of a pediatric nebulizer inaccordance with non-limiting examples.

FIG. 22 is another side sectional view of a different embodiment of apediatric nebulizer in accordance with the non-limiting example.

FIG. 23 is a sectional view of another embodiment of the nebulizer inaccordance with a non-limiting example and showing an airflow sensorsuch as a spinning fan wheel and associated with the main body, and awireless module that includes a processor and transceiver that canreceive measured airflow and wirelessly transmit data containingmeasured airflow to a separate device such as a handheld processingdevice in accordance with the non-limiting example.

FIG. 24 is a plan view of the nebulizer of FIG. 23 and showing an airflow sensor mounted within the air channel section of that nebulizer.

FIG. 25 is a cross-section view of another nebulizer configuration thatprovides air curtains and showing an air flow sensor mounted at themixing end of the nebulizer in accordance with the non-limiting example.

FIG. 26 is a fragmentary plan view of a handheld processing device thatcan be used in conjunction with the nebulizers having the airflowsensors and which can be configured to wirelessly receive datacontaining air flow measurements, such as for measuring and processingdata regarding the involuntary cough event.

FIG. 27 is a block diagram showing example components of a hand heldprocessing device such as shown in FIG. 26, which can receive data froma nebulizer containing air flow measurements.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Different embodiments will now be described more fully hereinafter withreference to the accompanying drawings, in which preferred embodimentsare shown. Many different forms can be set forth and describedembodiments should not be construed as limited to the embodiments setforth herein. Rather, these embodiments are provided so that thisdisclosure will be thorough and complete, and will fully convey thescope to those skilled in the art.

In accordance with a non-limiting example, the nebulizer because of itsconfiguration creates a differential pressure within an air channelsection between the venturi nozzle, medication reservoir and formed lowpressure mixing chamber when air is passed through the air line thatforms the venturi nozzle. Differential pressures in the nebulizer deviceoperate at a flow condition when at standard atmospheric pressure (STP),which causes no fluid or medication to flow through the nebulizeroutlet. As pressure decreases within the device during inhalation, i.e.,a negative inspiratory pressure, the differential pressure results inair flow and medication being drawn up from the medication reservoir fornebulization.

There are various mechanics of jet nebulizers that should be understood.A jet nebulizer is a device that is used to deliver medication to therespiratory system using a supplied air source. Traditional nebulizershave a vertical column of air passing through a reservoir of medication,which has a separation at the top of the nozzle allowing the air andmedication to mix. This mixture accounts for the initial medicationdroplet formation due to the drastic change in surface area andaerodynamic effects of the mixture region. This initial dropletformation can be estimated from a linear stability analysis and anaerodynamic loading analysis using parameters such as the Reynoldsnumber, Mach number, and Weber number. This initial droplet formation inthis region is normally not sufficient for the desired deposition of themedication in the respiratory tract. To further reduce the droplet size,these droplets travel at high speed and collide with a baffle. Thisimpact energy greatly reduces the droplet size to an acceptable levelfor deposition of medicine.

This traditional approach has several draw backs. One of the primaryfactors is that additional medication is required to deliver the properdose to the desired region of the respiratory tract. Droplet formationoccurs outside of the mouth in traditional devices and then has totravel through tubes, masks and the mouth. This additional travel periodallows more particle to particle interaction. These particle collisionsallow for particle combining, creating a larger diameter. Depositionwill not occur with these larger diameter droplets, and therefore wasteoccurs.

Reducing these particle interactions is possible using the nebulizer asshown in FIG. 1. This nebulizer operates to nebulize in the mouth andoperate as a horizontal nebulizer just outside of the mouth to allow forsmaller droplet sizes for deposition at a lower zone in the respiratorytract and use less medication, resulting in less waste.

The illustrated nebulizer operates such that the differential pressuresresult with the nebulizer operating at a flow condition when at standardatmospheric pressure. Nebulization does not occur. As pressure decreaseswithin the nebulizer due to inhalation, the differential pressuresresult in medication as fluid to flow up the nozzle.

Referring now to FIG. 1, there is disclosed an improved horizontalnebulizer 50 having a body 51 with a breath activated venturi nozzle 52that together with other components creates the differential pressurewithin an air channel section 54 when air is passed through the venturinozzle 52. The body 51 includes the air channel section 54 andmedication reservoir 58 and a nebulizer outlet 60 configured to bereceived within an oral cavity of the patient. The body is generallyhorizontally configured and includes a mouthpiece portion 62. In oneembodiment, a pacifier housing 64 is added as shown by the dashed line,to form a pacifier or lollipop configuration at the nebulizer outlet. Anair line 66 extends into the air channel section and includes theventuri nozzle 52 that is configured with the air channel section toform at its end a low pressure mixing chamber 68. FIGS. 2 and 3 show ingreater detail the air line and venturi nozzle that are configured withthe air channel section to form that low pressure mixing chamber, whichis somewhat conically shaped.

A primary suction line 70 extends from the medication reservoir 58 tothe low pressure mixing chamber 68 through which medication is drawnupward and mixed with air from the venturi nozzle 52 and nebulized fordischarge through the nebulizer outlet 60. A compressed air line 72 canconnect to the end of the body via an appropriate fitting 74. Theventuri nozzle, low pressure mixing chamber and air channel section areconfigured such that at standard temperature and pressure (STP), adifferential pressure results in no medication that is drawn upwardthrough the primary suction line for atomization, and none dischargedthrough the nebulizer outlet, until a negative inspiratory pressure iscreated from inhalation by a user.

As explained below, nebulization begins at a negative expiratorypressure from about −3 cmH₂O to about −52 cmH₂O. The venturi nozzle 52is positioned at a location to be placed within a patient's oral cavitywhen the nebulizer in use and received in the mouth of the user. Asillustrated, a rainfall chamber 76 is formed within the body 51 at theair channel section 54 into which the venturi nozzle 52 and low pressuremixing chamber are formed. As further illustrated, a diffuser 78 acts animpactor upon which the nebulized medication and air exiting the venturinozzle and low pressure mixing chamber impacts to aid in nebulization. Asecondary suction line 80 is formed within the rainfall chamber 76 anddraws nebulized medication that had dropped down after impacting thediffuser or impactor. A better view of the secondary suction line isshown in FIGS. 2 and 3. In another example, an airflow sensor 82 can bepositioned within the air channel section at the nebulizer outlet andconfigured to generate signals 83 indicative of air flow generated by apatient's involuntary cough event occurring at nebulization. A processor84 could be associated with the nebulizer or a separate unit such as ahandheld unit as shown in FIG. 26. This processor can receive signalsand evaluate the involuntary cough event as explained in greater detailbelow.

The dashed lines in FIG. 1 show that the nebulizer outlet can beconfigured as a infant pacifier and be formed as a housing or lollipop.In another example, it is possible for a housing to enclose the body andhave an end adjacent to the nebulizer outlet configured as an infantpacifier such as shown relative to FIGS. 21 and 22.

When the nebulizer is operating at a flow condition and at standardatmospheric pressure (STP), the differential pressures cause no fluidflow from the medication reservoir upward through the primary suctionline into the low pressure mixing chamber. As the pressure decreaseswithin the nebulizer due to inhalation, i.e., resulting from thenegative inspiratory pressure, the differential pressure results inmedication flowing up into the low pressure mixing chamber and airflowing through the venturi nozzle.

There is illustrated the medication reservoir 58 that includes theprimary suction line where the medication is drawn up into the lowpressure mixing chamber and air flows through the venturi nozzle. Thenebulizer includes a breath activated venturi. Although the venturi ispositioned for intra-oral use, it is not necessary to be in thatposition and can be located outside the oral cavity. The medication isreleased during breath activation as a horizontal nebulizer compared toan updraft style. Various medications could be mixed during the intakecycle. The nebulizer in accordance with a non-limiting example is animprovement over those prior art nebulizers that are actuated bypressing a valve for a user regulator while nebulizing.

In the nebulizer shown in FIG. 1, the flow through the venturi nozzle 52is not activated until there is a negative inspiratory pressure, such ascreated from inhalation by the patient. In this nebulizer, air pressureis continuous, but nebulization is not. The rainfall chamber 76 isprovided, but at STP, there is no flow of medication. At about −3 cmnegative pressure, the negative suction actuates air flow and medicationto be drawn upward through the primary suction line. When this occurs,the nebulized solution extends from the low pressure mixing chamber 68and impacts the diffuser 78, i.e., impactor and some droplets fall to bepicked up by the secondary suction line 80. There are no residual drops,condensation or agglomeration of nebulized medication that forms infront of the rain chamber, which could result in poor nebulization andair being drawn in by the patient. It is recirculated as a truenebulized medication.

In one example, the average pressure begins nebulizer operation at −52cm with a 2 liter a minute flow rate. It is possible to begin flow at −3cm negative pressure, but that has been found to be too sensitive. Inanother example, the nebulizer is configured to begin flow at −15 cmcorresponding to −1 bar. The venturi nozzle and other components of thenebulizer as shown in FIG. 1 can be designed to begin flow from −3 to−100 cm within the venturi nozzle. The nebulizer is a jet nebulizer thatrequires the negative inspiratory pressure to allow the venturi to beginoperating. The medicine fluid will not pass into the airstream until theflow begins through the venturi nozzle. Air is blowing at rest, but noventuri operation with flow occurs until a negative inspiratory pressureis supplied in front of the venturi nozzle at the air channel section toinitiate the venturi effect and draw the medication up into thejetstream at the low pressure mixing chamber. As long as the negativeinspiratory pressure is applied, there will be flow. If the negativeinspiratory pressure stops, there is no flow. One nebulizerconfiguration is for a 5 liter per minute air flow, but the nebulizercan be configured for 2 liter up to 15 liter air flow. When the venturinozzle begins operation, the medication hits the diffuser or impactorand some droplets fall downward and are drawn up by the secondarysuction line.

The nebulizer shown in FIG. 1 operates when there is negativeinspiratory pressure that activates the air flow through the venturinozzle and into the low pressure mixing chamber. It does not matter ifthe venturi nozzle is inside or outside the mouth. It is also not atimed type of nebulizer such as with processor monitored breathing orarranging nebulization based on breathing cycles and valves. With thenebulizer shown in FIG. 1, the patient inhales at a certain amount ofpressure and the air flow through the venturi nozzle. In one example, itis one bar corresponding to −15 cm of water. The average may be −53 cmand the first −15 cm could activates flow through the venturi nozzle.When inhalation pressure drops below −15 cm, then flow through a venturinozzle ceases.

FIG. 17 is a chart showing respiratory pressures for measured andpredicted MIP (maximal inspiratory pressure) and MEP (maximal expiratorypressure), as an example with the nebulizer shown in FIG. 1.

FIGS. 2-16 are sectional views of the nebulizer of FIG. 1 and showingthe air flow through the nebulizer of FIG. 1 at STE and differentpressures as showing the variations in pressure and air flow. A flow of2 L/min is illustrated in most of the diagrams and pressure gradientsare shown at STP and other pressures. These figures also show thepressure gradients and medication flow upward through the primarysuction line at different inspiratory pressures.

The nebulizer described in FIG. 1 can advantageously be used forpediatric patients, such as young children and infants. FIGS. 18 and 19show a nebulizer 100 in a pacifier configuration in which a rainfallchamber design as disclosed in the commonly assigned and incorporated byreference '306 patent includes an outer housing or body 102 that isconfigured similar to a pacifier or can be configured similar to alollipop.

This nebulizer in one example could be designed similar to the nebulizershow in FIG. 1 and be activated by negative inspiratory pressure. Inanother example such as shown in FIG. 20 of the nebulizer, a pressuresensor 104 positioned at the nebulizer outlet senses negativeinspiratory pressure. Upon sensing the negative inhibitory pressure, asignal is transferred back to a processor or controller or switch tooperate the nebulizer. In a preferred example, however, the nebulizershown in FIG. 1 is used, and there is no need to use a sensor with theassociated processor. If the configuration of FIG. 1 is used, thenegative inspiratory pressure begins the flow through the venturi nozzleand initiates medicine flow and nebulization.

The outer portion of the housing or body of the pacifier section of thenebulizer such as shown in FIGS. 19 and 20 includes a section that has aflavoring 106 and the position sensor 108 to indicate the infant's mouthposition. This flavoring section is advantageous for sensor placementwhen an infant sucks on the pacifier or lollipop configured nebulizer.The infant or child will naturally suck on those areas of the pacifierthat have the flavoring, indicative that the infant has positioned thepacifier nebulizer in its mouth in the proper position to allownebulization to occur. When the infant or child has received thepacifier nebulizer in its the proper position as indicated by the sensorindicating this position, the lips or other portion of the infant'smouth covers the position sensor to indicate the proper mouth position.The position sensor sends a signal back to a controller, for example, toactivate the nebulizer for operation. Operation in one example occursonly when the pressure sensor senses the negative inspiratory pressure.In the venturi nozzle design of FIG. 1, however, the negativeinspiratory pressure itself begins the air flow through the venturinozzle and medication to be draw upward.

As illustrated, if a nebulizer other than that shown in FIG. 1 is used,the flavoring on the outer portion of the pacifier allows an infant orchild to position the pacifier nebulizer in its proper position in itsmouth to allow nebulizer operation since the infant or child willnaturally position the pacifier in a position where it can sense theflavor. A sugar-free flavoring can be used.

When this occurs, the infant will activate the position sensor thatindicates the pacifier is in the proper position in the mouth for fullnebulization and it effects. This activates the nebulizer for operation.The other pressure sensor within the intake would sense the negativeinspiratory pressure, which then would send a signal back to a processoror controller or switch that is connected to any valves and/or medicinereservoirs and air lines to operate the nebulizer. Valves could open toallow operation in this example.

FIG. 18 shows a configuration in which the pacifier is received withinan infant's mouth. The rainfall chamber portion is contained within thenebulizer or lollipop configured body or housing as a nebulizer suctionmember formed from a flexible material, as shown in FIGS. 19 and 20,while the other sections of the nebulizer in the '306, patent such asthe medicine reservoir and any other type of medicine containers arecontained in a separate housing or body that could be configured similarto a choo-choo train or other infant toy.

Also, the use of more than one medicine container with differentmedicines can allow simultaneous treatment or delivery of differentmedicines, actually creating a new drug based upon the combination. Itis possible to change the combination depending on infant and childneeds. Thus, with the configuration of FIG. 1 an infant can inhalecreating the negative inspiratory force to activate the nebulizer, whichbecomes breath activated in this example. Other configurations can beused where inhalation can cause the nebulizer to open with differentvalves depending on the design.

FIG. 20 shows a nebulizer configuration such as described in theincorporated by reference '306 patent in which the nebulizer includesthe rainfall chamber 110 and venturi 112 and medicine feed lines 114.Although not illustrated, the nebulizer could include a reservoir ofmedicine and would include at a distal end beyond a medicine port an airintake for an air line feeding the venturi inside the nebulizationrainfall chamber. The medicine for the nebulizer can be filled directlyinto the reservoir or the nebulizer can come preloaded with themedicine. A venturi air line 116 could include a patient air intake portthat allows air to be taken in at that port and fed through the body ofthe nebulizer. A cap could cover a medicine reservoir and be screwed on,snapped on, or otherwise locked on. The cap could be constructed somedicine could be injected into the reservoir through the cap.

FIG. 20 shows the side sectional view of the end of the pediatricnebulizer that engages the patient's mouth in accordance with one aspectof the invention, showing in more detail the rainfall chamber 110 andthe venturi 112 and medicine feed lines 114. The venturi nozzle isapproximately in the center of the illustration. Right beneath theventuri nozzle is a chamber which is fed by a venturi air line,indicated at the lower portion of the figure to the left of the venturichamber. Parallel to the venturi air line and located somewhat displacedabove the venturi air line is the medicine feed line 114. Medicine fromthe reservoir flows through the medicine feed line and through arelatively small opening just prior to the venturi in order to dispensemedication into the air flow of the venturi. The venturi effect causes areduction in pressure which causes the medicine to flow from thereservoir through the medicine feed line and into the venturi spacewhere it is mixed with the air in traditional venturi fashion. Themedicine that is nebulized by action of the venturi is expelled from theventuri port in an upward direction toward the diffuser 120. Thediffuser in this case, is shown as textured. It is not necessary that itbe textured but texturing may facilitate the break up of the dropletsfrom the venturi into smaller sizes. As the droplets from the venturibounce off the diffuser and break up, the sizes may not be totallyuniform. The air pressure, the feed rate, the velocity with whichdroplets impact the diffuser and other well known factors can facilitateproduction of droplets of desired sizes. In fact, droplets can begenerated utilizing this arrangement in sizes less than 0.1 microns.Nevertheless, larger droplets may coalesce as they diffuse throughoutthe rainfall chamber space. As droplets coalesce, they become larger andfall toward the bottom of the chamber where medication that is notutilized is gathered in a recycle sump 122. Medication found in therecycle sump, is recycled through the recycle venturi port 124 to theproximity with the venturi intake to be reutilized. In this manner, verylittle medication is wasted and the amount of medication delivered tothe patient can be tightly controlled.

When the infant places his mouth on the patient inhale port, air fromthe infant inhale air path will circulate over the rainfall chamber andaround the diffuser causing the extraction of droplets from the rainfallchamber for delivery to the patient. The patient inhale air path may gonot only over the rainfall chamber but around it to either side with theactual sizing depending upon the need for the amount of air flow to bedelivered to the patient during administration of medication.

Dose reliability and reproducibility is enhanced by using unit dosemedicine containers. High lung-deposition efficiency is vastly improvedover the prior art because the venturi is located near or preferablyinside the oral cavity. Very fine particles can be produced inaccordance with the invention.

FIG. 20A shows a more complete view of the nebulizer as shown in FIG.20, which also includes an air flow sensor 130 within the patient airflow channel. The pediatric nebulizer that incorporates this designcould include air flow sensing ability to determine the capabilities ofthe infant as to one capacity and other details, but also give anindication of response, if necessary, to an involuntary reflex coughtest. The air flow sensor could be connected by a wireless interfacewith a processor and transceiver such as shown in FIG. 23 and describedbelow. Thus, functional components as shown relative to FIG. 23 can alsobe included in the nebulizer such as shown at FIG. 20A.

FIGS. 21 and 22 show other nebulizers configured for pediatric use. Theventuri can be designed for breath activation as described before.Although the suction line is illustrated as a primary suction line, itshould be understood that a secondary suction line can be used. FIG. 21shows a nipple configuration and FIG. 22 shows a lollipop configuration.

FIG. 21 shows a different configuration for the nebulizer 100 thatincludes a mouth guard 110 and a suction line with the air lineattachment. A different type of impactor/fractionator is disclosed andthe nebulized medicine will impact against the impactor/fractionator andbe discharged though the orifice at the nipple. The drops are spreadthroughout the open area defined by the pacifier housing. In anotherexample, the nebulizer can operate in timed sequence to permitnebulization at specified times. A mouth guard is also illustrated.

FIG. 22 shows a modified lollipop configuration in which the air lineattachment is shown in the primary suction line with the interiorsurface of the lollipop housing forming the impactor/fractionators tocreate greater fractionation. It is possible to insert a flow meterdevice such as a fan wheel that can operate to determine air flow fortesting purposes. The air flow sensor could be connected to a smallprocessor or communicate with a plug in in which a handheld device suchas shown in FIG. 23 can be plugged into the rear of the lollipopconfigured nebulizer.

It should also be understood that new medicines can be designed by useof the venturi system. It is possible to preload the drug and form a newdrug as a method. The nebulizer could operate as a trihaler orquadhaler. It can be placed in a solution in one container as a new drugand combined with a delivery system. It is possible to form thenebulizer and preload with the drug. Blow, fill and seal technologycould be used to form a throw away nebulizer that is used one time. Itcould be filled and sealed at the manufacturing line. There could be aprefill port of any different shape or form and different types ofmedication delivery configurations. An example of differentconfigurations for medicine supply as shown in FIGS. 15 and 16 of the'602 published patent application.

The use of a second nozzle can be advantageous because when condensationor agglomeration occurs, a drug will drop down through gravity feed andbe redrawn to aid in mixing especially with preloaded medicine. Thus,the nebulizer shown in FIG. 1 can be formed as a sterile preloadedmedicated nebulizer as a throw away device. Multiple new drugs can bedeveloped through mixing with the nebulization and a venturi action.

It is also desirable to incorporate a flow meter function as describedin the copending U.S. Ser. No. 12/724,785. This incorporated byreference patent application shows two types of flow meter designs thatcould operate as a clip-on device onto the various nebulizers disclosedand incorporated by referenced patents identified above. Other designsare in-line and are the preferred design with the nebulizerconfigurations shown in FIG. 1 or any pediatric nebulizers. In onedesired design a spinning wheel is used instead of the designs show inthe incorporated by reference application. In the embodiments describedin the instant application, the nebulizer can be used to measureinvoluntary cough and measure the expiatory flow for the voluntary coughand what is the response. This could be beneficial with the pediatricnebulizer using the pediatric nebulizer for diagnoses. A spinning wheelfor some type of spirometers could be incorporated into the nebulizersand used with the C5 stimulus, in which the involuntary cough occurs onthe average of 4.8 times (average of 5 times) or 4.8 seconds on anaverage. The spinning wheel can calibrate a processor to measure peakflow and time over the inspiration and expiration and form a graph. Itis possible to form the nebulizer where a button is pressed to activatethe nebulizer, resulting in the involuntary cough. A flow sensor can beintegrated with the nebulizer measures air flow at the time of theinvoluntary cough or at the time the button is hit. It is possible toplug the hand held device into the nebulizer as illustrated. Thenebulizer device can perform the pulmonary function test (PFT) that isadequate for use with kids, such as using the lollipop nebulizer asshown in FIG. 21. It is possible to measure the velocity of the airflowand draw a graph of the inspiration and expiration over time. The systemcan draw loop interfaces to the processor or other PC and be comparedrelative to voluntary cough. During the C5 event it is possible toestablish the normal versus the abnormal range.

Reference is made to the commonly assigned and incorporated by referenceU.S. Patent Publication Nos. 2011/0040157; 2011/0046653; and2011/0040211, the disclosures which are hereby incorporated by referencein their entirety. It is possible to diagnose GERD and perform otheranalysis as explained in those incorporated by reference patentapplications, including diagnosing stress urinary incontinence andproblems with the lower esophageal sphincter.

The flow meter could be formed within an extension as a collar or moldedinto the nebulizer itself.

There is now described the nebulizers and flow meter sensor relative toFIGS. 23-27, similar to the description taken from the incorporated byreference Ser. No. 12/724,785 application.

FIG. 23 shows a nebulizer 204 that includes the main body 200 having anair channel section 201 that is formed by the air line intake 300 andfluid/air channel section 230 and related sections of the main body asillustrated and including a mixing chamber 330 and venturi 310positioned to be placed within close proximity or within the patient'soral cavity in this non-limiting example and configured to receivemedicine and air and mix the medicine and air within the mixing chamberand receive the air flow through the venturi and cause the medicineentering the mixing chamber to be atomized by the action of air flowingthrough the venturi. In this embodiment, an air flow sensor 280 isassociated with the main body, and in this example at diffuser 250, andconfigured to measure the air flow created by the patient's one of atleast inhaling and exhaling air. In this example, the air flow sensor280 is positioned within the air channel section 330 and as illustratedat the exit side of the mixing chamber within the diffuser such that airflow is measured when the patient is at least one of inhaling andexhaling air through the diffuser in this example.

The air flow sensor 280 senses and measures the air flow and sends asignal through communications signal lines 282 (shown in FIG. 24) backto a wireless module 284 positioned in the main body 200. The wirelessmodule 284 in this example includes a processor 286 and wirelesstransceiver 288 such that the signals from the air flow sensor 280 areprocessed and in this example wirelessly transmitted through an antenna289 (which could be a conformal antenna positioned on the main body 200)to a handheld processing device 560 such as shown in FIG. 26 and withits processing capability illustrated in block diagram at FIG. 27. Theoutlet at the diffuser on the exit side of the mixing chamber in thisexample chamber includes an air flow metering valve 290 positionedwithin the air flow channel and configured to adjust the resistance toair flow to a predetermined level for respiratory exercise training andincentive spirometry use. In this example, the air flow metering valve290 is formed as a baffle or similar mechanism that can be adjusted tovary the amount of air flow resistance. The adjustment can be indexedsuch that any adjustment and air flow resistance can be predetermined,for example, using a manual adjustment or servo drive (actuator) foradjusting the valve. The air flow sensor 280 in this non-limitingexample is shown as paddle wheel type sensor or could be a flap withactuators, such as MEMS actuator, which inter-operate with a processorto determine air flow adjacent the air flow metering valve 290. The airflow metering valve 290 in an example includes a small drive mechanismsuch as an actuator attached thereto, allowing adjustments to be madebased upon a signal such as from the processor 286 and feedback signalfrom the air flow sensor to adjust and vary the amount of resistance toair flow for respiratory exercise training and incentive spirometry use.The valve 290 can also in one example be manually adjusted by a patientand include settings to aid in adjustment as noted before.

In a non-limiting example, the handheld processing device 560 isconfigured to process the measured air flow over time to determine arespiratory function of the patient. This device 560 is also configuredin another example to process measured air flow over time to determine aneurological deficiency in a patient based on air flow measurementsderived from an involuntary reflex cough. For example, the analysis ofthe voluntary cough and involuntary reflex cough test is disclosed incommonly assigned and U.S. Patent Publication Nos. 2007/0135736;2010/0137736; 2007/0255090; 2010/0137737; 2011/0040157; 2011/0046653;and 2011/0040211, the disclosures which are hereby incorporated byreference in their entirety. These commonly assigned published patentapplications set forth details of the voluntary cough testing andinvoluntary reflex cough testing in which the nebulizer as described inthe instant application can be used to aid in the type of testing as setforth in those incorporated by reference applications. Such testing isadvantageously used to diagnose stress urinary incontinence or problemsin the lower-esophageal sphincter as a non-limiting example.

FIG. 25 shows a modified nebulizer such as the type disclosed incommonly assigned U.S. Publication No. 2007/0137648, the disclosurewhich is hereby incorporated by reference in its entirety. Thisapplication shows air curtain inlets created by air curtain conduits 404that are used to supply a curtain of air above and below the nebulizedmedicine and air passing through medication conduit 400 and to enhancepenetration of nebulized medicine into the airway of the patient. Theair flow sensor 280 as a paddle wheel type device is positioned at theexit end of the nebulizer 204 as illustrated and in this exampleincludes the air flow metering valve 290 as illustrated and incorporatesa manual or automatic adjustment mechanism such as an actuator as may beneeded.

It should be understood that different types of air flow sensors 280 canbe used besides the illustrated spinning wheel configuration. Asdisclosed in the incorporated by reference 2010/0204602, it is possibleto design the air flow sensor 280 as a mass air flow sensor thatconverts the amount of air drawn or expelled into and out of thenebulizer into a voltage signal. Different types of mass air flowsensors could be used such as a vane air flow meter, including using anynecessary MEMS technology or using a Karmen vortex or a semiconductorbased MAF sensor. It is possible to use a hot wire MAF sensor such as athermistor, platinum hot wire or other electronic control circuit tomeasure temperature of incoming air, which is maintained at a constanttemperature in relation to the thermistor by an electronic controlcircuit. As heat is lost, electronic control circuitry can compensate bysending more current through the wire. This is only one example. Thewire typically will be kept cool enough such that the temperature doesnot impact a patient. The hot wire can be placed further into thediffuser and/or main body within the air channel. It is also possible touse an Intake Air Temperature (IAT) sensor.

Another possible air flow sensor is a vane air flow meter that includesbasic measuring and compensation plates and other potentiometercircuits. In another example, the air flow sensor uses a “cold wire”system where an inductance of a tiny sensor changes with the air massflow over that sensor as part of an oscillator circuit whose oscillationfrequency changes with sensor inductance. In another example, the flowsensor is an electronic membrane placed in the air stream that has athin film temperature sensor such as printed on an upstream side andanother on the downstream side and a heater in the center of themembrane that maintains a constant temperature similar to the hot-wire.Any air flow causes the membrane to cool differently at the upstreamside from the downstream side and this difference indicates the mass airflow. MEMS technology can be used such as MEMS sensors. In this type ofsensor, a MEMS sensor has a silicon structure and sometimes combinedwith analog amplification on a microchip. It includes ananalog-to-digital converter on a chip in another example and can befused with analog amplification and the analog-to-digital converters anddigital intelligence for linearization and temperature compensation. TheMEMS testing in one example is used for an actuator to control the valve290.

It should be understood that although the air flow sensor is shownlocated at the discharge end of the nebulizer at the diffuser on theexit side of the mixing chamber, other locations and positions for theair flow sensor or number of air flow sensor members are possible aswell as the valve 290.

It should also be understood that the nebulizer using the waterfallchamber as described in incorporated by reference patent publicationsalso in an example has the flow meter function as described and includesthe air flow sensor and wireless module as illustrated in FIGS. 23 and24 and can be positioned in different locations within that device. Theair flow sensor can be located at the discharge end on the exit side ofthe rainfall chamber or other locations in which the air flow can bemeasured. The valve 290 is also included in another embodiment andincludes an actuator in yet another embodiment.

Air flow can be measured in pounds per second (lbs./sec.) and operatefor pulmonary function testing calculations and incentive spirometryuse. The nebulizer in this example can work as a differential pressuretransducer and connect to a pneumotachygraph (or have a self-containedchip with such function) to record the velocity of respired air. It ispossible to process associated data as air flow, air pressure, airresistance, and other Pulmonary Function Testing (PFT) results forrespired air and data results from voluntary cough (VC) and involuntaryreflex cough testing (iRCT). The pulmonary function testing can usespirometry to assess the integrated mechanical function of the lungs,chest wall and respiratory muscles and measure the total volume of airexhaled from a full lung for total lung capacity and empty lungs asresidual volume. The Forced Vital Capacity (FVC) can be measured and aforceful exhalation (FEU can be repeated. Spirometry can be used toestablish baseline lung function, evaluate dyspnia, detect pulmonarydisease and monitor effects of therapies used to treat respiratorydisease and evaluate respiratory impairment and evaluate the operativerisk and perform surveillance for occupational-related lung disease.Pulmonary function testing can be used to determine how much air volumeis moved in and out of the lungs and how fast the air in the lungs ismoved in and out. This testing can determine the stiffness of the lungsand chest wall for compliance. The flow meter function using the airflow sensor and the associated air flow metering valve together with anyprocessing capability can be used for Inspiratory Muscle Training (IMT)to provide consistent and specific pressures for inspiratory musclestrength and endurance training. The adjustable valve or otheradjustable mechanism can ensure consistent resistance and be adjustablesuch as manually or through microprocessor control for specific pressuresettings. It is possible to use the same nebulizer for exercisetreatments and therapy and spirometer treatments. The handheldprocessing device 560 captures the data and can be marketed togetherwith the nebulizer and any necessary catheters for reflex cough testingas a kit. The pneumotachygraph function can be placed in a single chipwithin the nebulizer or as a separate flow meter device explained belowrelative to FIG. 25 and connected to the nebulizer. Data containing airflow measurement results can be wirelessly transmitted to the handheldprocessing device or other processor.

The nebulizer also operates in a non-limiting example as a differentialpressure transducer. If the nebulizer is to measure voluntary cough orthe involuntary reflex cough, an air channel can be connected to themedicine and gas canister (for tartaric acid in one example) and measurethe voluntary cough and involuntary reflex cough for in-phase durationfrom the time from onset to peak and expulsive phase and in-phase volumesuch as the duration of the glottic closure as explained in greaterdetail below. It is also possible to measure in-phase peak flow and theexpulsive phase peak flow using such device.

A patient (or clinician or physician) can perform a medical treatmentwith the nebulizer. It is also possible to operate the flow meter afternebulization to determine if the patient has improved due to the use andadministration of the drug such as the tartaric acid. It is possible tomeasure and graph results through an air flow sensor as part of the flowmeter device and transfer data to the handheld device (or otherprocessing device) and measure flow and pressure over time.

FIG. 26 is an illustration of an exemplary handheld processing device560. More particularly, it should be understood that this handheldprocessing device 560 can be used by a nurse practitioner or doctor andreceive input as wireless signals for flow meter testing as describedabove. Also, this handheld processing device 560 can incorporate thecircuit and functions as disclosed in the various copending and commonlyassigned applications identified above. Catheters and other inputs canbe connected to this handheld processing device 560 as explained in theabove-identified and incorporated by reference patent applications.

FIG. 27 is a block diagram that illustrates a computer system 500 forthe handheld processing device 560. Computer system 500 includes a bus502 or other communication mechanism for communicating information, anda processor 504 coupled with bus 502 for processing information.Computer system 500 also includes a main memory 506, such as a randomaccess memory (RAM) or other dynamic storage device, coupled to bus 502for storing information and instructions to be executed by processor504. Main memory 506 also may be used for storing temporary variables orother intermediate information during execution of instructions to beexecuted by processor 504. Computer system 500 further includes a readonly memory (ROM) 508 or other static storage device coupled to bus 502for storing static information and instructions for processor 504.

Computer system 500 may be coupled via bus 502 to a display 512, such asa LCD, or TFT matrix, for displaying information to a computer user. Aninput device 514, for example buttons and/or keyboard, is coupled to bus502 for communicating information and command selections to processor504. Another type of user input device is cursor control, such as amouse, a trackball, or cursor direction keys for communicating directioninformation and command selections to processor 504 and for controllingcursor movement on display 512. This input device typically has twodegrees of freedom in two axes, a first axis (e.g., x) and a second axis(e.g., y), that allows the device to specify positions in a plane.

Computer system 500 operates in response to processor 504 executing oneor more sequences of instruction. Execution of the sequences ofinstructions causes processor 504 to perform the process steps describedherein. In alternative embodiments, hard-wired circuitry may be used inplace of or in combination with software instructions to implement theinvention. Thus, embodiments of the invention are not limited to anyspecific combination of hardware circuitry and software.

The term “computer-readable medium” as used herein refers to any mediumthat participates in providing instructions to processor 504 forexecution. Such a medium may take many forms, including but not limitedto, non-volatile media, volatile media, and transmission media.Non-volatile media includes, for example, optical or magnetic disks.Volatile media includes dynamic memory, such as main memory 506.Transmission media includes coaxial cables, copper wire and fiberoptics, including the wires that comprise bus 502. Transmission mediacan also take the form of acoustic or light waves, such as thosegenerated during radio wave and infrared data communications.

Common forms of computer-readable media include, for example, a floppydisk, a flexible disk, hard disk, magnetic tape, or any other magneticmedium, a CD-ROM, any other optical medium, a RAM, a PROM, and EPROM, aFLASH-EPROM, any other memory chip or cartridge, a carrier wave asdescribed hereinafter, or any other medium from which a computer canread.

Various forms of computer readable media may be involved in carrying oneor more sequences of one or more instructions to processor 504 forexecution. For example, the instructions may initially be carried on amagnetic disk of a remote computer. The remote computer can load theinstructions into its dynamic memory and send the instructions over atelephone line using a modem. A modem local to computer system 500 canreceive the data on the telephone line and use an infrared transmitterto convert the data to an infrared signal. An infrared detector canreceive the data carried in the infrared signal and appropriatecircuitry can place the data on bus 502. Bus 502 carries the data tomain memory 506, from which processor 504 retrieves and executes theinstructions. The instructions received by main memory 506 mayoptionally be stored on storage device 510 either before or afterexecution by processor 504.

The handheld device 560 preferably uses wireless technology that couldinclude infrared (IR), Bluetooth, or RFID technology for communicatingwith the wireless transceiver in the wireless module of the nebulizer ora separate wireless interface as illustrated. It can be connecteddirectly also. The handheld processing device 560 includes a wirelessmodule 580 that works in conjunction with the pressure transducerinterface and controller 518 and the respiratory air flow sensor (flowmeter) interface 581 and sends and receives readings through the antenna582 or other system that could be used. The wireless module 580 could belocated at different locations.

For purpose of technical instruction, there now follows a generaldescription of physiology for the involuntary reflex cough test (iRCT),which activates the Nucleus Ambiguus, which is also disclosed in some ofthe incorporated by reference patent applications. The nebulizer withthe flow sensing function is adapted for measuring both voluntary coughand involuntary reflex cough, such as explained in the incorporated byreference patent applications. The iRCT selectively activates the MedialMotor Cell Column (MMCC) of the spinal cord rather than the (Lateral)LMCC to fire muscles embryologically predetermined to be involuntarycough activated muscles in the pelvis. In the past, urologists did notselectively activate MMCC without overtly activating the LMCC. Magneticstimulation or electrical spinal cord stimulation activate both cellcolumns and thus it is not possible to sort out pathology with these.Magnetic stimulation or other approaches from CNS activation set offboth columns.

The pelvic muscles that typically are activated with MMCC coughactivation include the lumbar-sacral L5/S1 paraspinal axial musculature,which facilitates inpatient continence screening. An example is throughMMCC iRCT muscle activation, obtaining L5/S1 paraspinal firing but notL5/S1 lateral gastrocnemius activation because the gastroc muscles arelimb muscles activated primarily through the LMCC.

The L-S paraspinals are easier to access with a large pad placed abovethe sacrum on the midline that contains active, reference and groundcombined. It is not important to determine lateralization of theactivity like needle EMG for radiculopathy, but only if activationoccurs reflexively where the onset latency is under the pressureactivation of the abdomen such as the Levator Ani. This is a poor musclefor these purposes because people train it to activate and set theirpelvis if the person senses any intra-abdominal pressure elevation.Also, it is difficult to get pads to stick to that area with hair,perspiration, fungal infections or bowel/bladder incontinence present,and other factors.

Some examples have been developed and studied, including a normal CNSpatient with Lumax bladder and bowel catheters and pads at L5/S1paraspinals and a separate EMG machine and electrodes at the pelvicfloor in a standard 3:00 and 9:00 o'clock set-up to demonstratesimultaneous involuntary activation with iRCT. This sets off the pelvicfloor muscles. Thus, normal airway protection data is obtained andnormal CNS data to L1 (where spinal cord ends). The set-up includes acomplete T12 that cannot void and needs intermittent catheterizationwith the same set up, thus demonstrating data for normal airway but noL5/S1 EMG activation by MMCC with all the other data necessary to provean unsafe bladder by the algorithm. A quadriplegic can demonstrateabnormal airway protection and abnormal EMG activation at bothparaspinal and pelvic floor muscles with unsafe bladder measurementsthat follow the algorithm.

It should be understood that iRCT is an involuntary maneuver thatactivates embryologically predetermined muscles for airway protectionand continence that travel primarily through the MMCC in the spinalcord. Different varieties of lesions are captured and determined withsummated interval data approach for general screening purposes.

It is known that the laryngeal cough reflex (LCR) is a strongbrainstem-mediated reflex that protects the upper airway by preventingaspiration, or the entrance of secretions, food, and/or fluid into theairway below the level of the true vocal cords (rima glottidis), throughelicitation of an involuntary cough. The LCR is activated through thestimulation of cough receptors in the vestibule of the larynx. One waythis is achieved is through the inhalation of chemostimulants, such astartaric acid. Studies have shown that if the LCR is intact, the subjectwill involuntarily cough (normal LCR) upon inhaling a solutioncontaining TA.

In one non-limiting example, the iRCT involves the inhalation of anebulized 20% normal saline solution of L-TA (Tartaric Acid). Subjectsare asked to perform 1 to 3 effective, full inhalations (about 15-20second exposure by mouth for tidal breathing wearing a nose clip) from astandard jet nebulizer with at least 50 psi from an oxygen wall unit ortank that produces an average droplet diameter of 1 to 2 microns orless. The nebulizer output is 0.58 mL/min. The initiation of aninvoluntary cough reflex after any one of the inhalations is the endpoint of the procedure.

Nebulized TA is a chemical tussive that stimulates irritant receptors inthe mucosa of the laryngeal aditus. Mild irritation of these receptorsresults in nerve impulses being conveyed by the internal branch of thesuperior laryngeal nerve (ibSLN) to bulbar centers of the brainstem.This nerve constitutes the afferent sensory component of the LCR arc.The efferent component of the LCR is mediated through the vagus,phrenic, intercostals and thoracoabdominal nerves.

Inhaled TA is selective in stimulating rapidly adapting (“irritant”)receptors (RARs), in the supraglottic region. In humans, bilateralanesthesia of the ibSLN abolishes TA-induced cough and permits tidalbreathing of the nebulized vapor without coughing, supporting the ideathat the RARs are responsible for TA-induced cough.

The physiological response from inhalation of TA in a normal subject isabrupt, forceful coughing of short duration. Using a 20% solution ofinhaled nebulized TA is a safe, reliable way to assess the sensation inthe supraglottic laryngeal region and subsequently the neurologiccircuitry of the LCR. In addition, the ability of the iRCT to predictthe integrity of the protective LCR in subjects with stroke has beenstudied.

A 20% solution of TA as an aerosol causes cough by stimulating sensorynerves in and under the laryngeal epithelium. These nerves have beenidentified histologically, and the reflexes they cause have beenidentified. The sensory nerves can be stimulated by both non-isosmolarand acid solutions. Tartaric acid may act in both ways, but the balancebetween them is uncertain.

The nerves are stimulated by the opening of membrane channels in thenerve terminals. More than 20 categories of channels have now beenidentified, the opening of which will allow calcium flow into the nerve(and also sodium, with exit of potassium), with the result that anaction potential is set up, which travels to the brainstem in thecentral nervous system (CNS), and reflexively induces cough.

Several different types of sensory nerve ending in the larynx have beenidentified that may mediate cough and other defensive reflexes. Theyhave been extensively studied, mainly in experimental animals byrecording the action potentials in their nerve fibers. The probablecandidates for cough are the RARs or ‘irritant’ receptors. These arehighly sensitive to mechanical stimuli, to hyperosmolar solutions, andto acids.

Once stimulated, the sensory nerves will induce a variety of defensivereflexes, which protect the lungs from invasion of harmful material.These include cough (an inspiration, followed by a forced expirationagainst a closed glottis, followed by opening of the glottis with anexpiratory blast); the laryngeal cough expiratory reflex (LCER, apowerful expiratory effort with the glottis open); and the glottalclosure reflex. In some instances a reflex apnea can be produced. Thebalance of these reflexes may depend on the nature and the strength ofthe stimulus. In the case of TA, the LCER seems to be dominant, possiblyfollowed by glottal closure, and the pathophysiological advantage ofthis response in preventing aspiration is obvious.

There now follows an analysis and test results in greater detail thatexplain the advantageous use of the involuntary reflex cough test (iRCT)for investigating and diagnosing not only SUI, but also physiologicalabnormalities such as neurologic deficiencies. The nebulizer asdescribed can be used in conjunction with testing. It should beunderstood that there are differences between normal and neurologicalpatients.

The EMG from the parineal muscles respond almost simultaneously to theonset of the voluntary cough because the patient does not want to leak.With the involuntary reflex cough test, on the other hand, the fastfibers that are set off reach the abdominal muscles quickly, such as in17 milliseconds as an example. The patient is not able to set theirpelvis. In some of the graphs reflecting urodynamic testing as will bedescribed, it is evident that the onset of the EMG activity does nothappen at the same time the pressure rises. Some people that haveneuropathy, for example, spinal stenosis or nerve injury (even if it ismild), have a situation that prevents the reflexes from closing beforethe pressure has changed to push on the bladder. It is not possible toobtain this diagnostic tool methodology unless the involuntary coughreflex test is accomplished. When the involuntary reflex cough test isaccomplished, it is possible to demonstrate a latency delay and showthat the pathophysiology is a neuropathic problem rather than astructural problem. It is possible to separate the pathophysiology usingthe involuntary reflex cough test and methodology as described.

In one example, a female patient could have a weak spinal cord and herphysiology is normal. This patient may not leak during the test, but thepatient cannot protect her airway. Thus, using the methodology apparatusand system associated with the involuntary reflex cough test, inaccordance with non-limiting examples, it is possible not only todiagnose an unprotected airway, but also to diagnose normal bladderphysiology, including the neurophysiology to the patient's sphincterclosure process. This is advantageous because it is then possible todetermine when someone cannot protect their airway, even though they mayhave a normal bladder. Conversely, there are patients with a normalairway, but cannot control their bladder. This process and system asdescribed is able to make that diagnosis and thus the involuntary reflexcough test is an advantageous medical diagnostic tool. For example, itis possible to have a patient with a poorly functioning bladder andnormal airway and use of the test allows a doctor to find lower urinarytract symptoms and neuropathology. It becomes possible to diagnose alevel of lesion in a patient with a full comprehensive neurologicexamination using the involuntary reflex cough test, methodology andapparatus as described.

As will be described in detail later, the various components such as thenebulizer, one or more catheters, any pads for the paraspinal muscleswhen EMG is used, and drug as part of the nebulizer are inserted in akit for use at the clinic, hospital or setting. Those components can bediscarded after use. The handheld device, of course, will be used again.Use of the kit provides a clinician, doctor or other medicalprofessional the readily available diagnostic tool to determine if apatient has a questionable airway and determine bladder physiology atthe same time, all with the use of the one kit.

A kit that is marketed for the iRCT diagnostic tool could include thenebulizer and its drug as TA in one example and one or more pads for theelectrodes at the paraspinal and use with EMG. The pad may only benecessary for stress incontinence determinations. A catheter is includedin another kit example for use in measuring airway and intra-abdominalpressure. In one non-limiting example, a pad can be placed on a catheterto determine urine leakage and aid in determining stress incontinence.Pressure data is sent to the handheld device in some examples. Obtainingany EMG values from the paraspinal in conjunction with the urologyanalysis is advantageous. It is possible in one example to measurepressure from a bladder catheter and determine at the same time EMGsignals using the EMG electrodes at the L5/S1 in conjunction with themeasured involuntary reflex cough test and urology catheter sensing.This is advantageous compared to placing electrodes at the perinealmuscles on each side of the sphincter.

It has been found that EMG signals obtained from the perineal muscleshave EMG activity from the non-involuntary muscles, i.e., the voluntarymuscles blacking out and making analysis difficult because of the signalinterference. When the electrodes are placed at the back at the L5/S1junction, on the other hand, there is nothing else but the paraspinalmuscles. It is bone below on each side at the L5/S1 junction. Theelectrical impulses can be obtained that determine the number of coughimpulses coming down through the patient. This is accomplished even if aperson has much adipose. The electrode pad used at the L5/S1 junction,in one non-limiting example, typically has an active reference andground. A pad holds this active reference and ground and the leads asthe active reference and ground are plugged into the handheld device (orwireless sensing device in another example) and transmit data to theprocessor. At least one catheter is also plugged into the handhelddevice (or wireless sensing device) and measures bladder pressures. Arectal catheter can also be used in some examples. The processorreceives EMG signals and determines when the cough event is over.

The involuntary coughs are not hidden by interference when measured fromthe lower back at the paraspinals as described. This allows a clinicianto determine coughs from the bladder when the EMG located at the L5/S1.In one aspect, the area under curve and the average pressure isdetermined for the cough event corresponding to the involuntary reflexcough test. When this involuntary component of the cough ends, in oneexample, it becomes silent EMG activity for a period of time. Thepressures are at baseline for a period of time, which corresponds in oneexample to an inhalation. The involuntary component is over.

Sometimes with the involuntary reflex cough test, the cough occurs sixtimes without breathing, but when the patient stops to breathe, theevent is over. Using the programming applied with the processor in thehandheld device, it is possible to calculate the variables inside thewave as to the involuntary cough and determine airway protectioncapability. Thus, it is possible to determine and measure cough bydefining through appropriate data processing the involuntary cough eventcompared to the whole cough epoch. For example, a patient could coughten times, but only the first four are part of the involuntary coughevent. The coughs after that event are not part of the epoch.

The programming includes algorithm branches resulting in a conclusion ofunsafe bladder based on the data analysis. It is possible to calculatefrom the waveforms information necessary for assessing airway protectionability. It should be understood that taking the EMG from the L5/S1 isalso a better situation for the doctor or clinician, and the patient,since it is more acceptable in a hospital, outpatient or inpatientsetting. The doctor or clinician does not have to bend down or stoop andlook near the crotch area and place pads since the EMG can now be takenfrom the paraspinals. Also, the placement of pads and electrodes at theparaspinals is advantageous when patients are standing. If pads areplaced at the perineal area, sweat and other problems could cause thosepads to become loose and good signals may not be obtained. Also, itshould be understood that the perineal muscles do not fireinvoluntarily. The sphincter may fire involuntarily, but that wouldcreate more noise as noted before. Electrodes are not placed at thevagina, but are placed at the paraspinal area instead.

This information obtained from iRct and the EMG taken at the paraspinalsallows the doctor or clinician to obtain data leading directly to adiagnosis. For example, some patients that have urinary stressincontinence may have a normal airway in this analysis. It has beenfound by experimentation that the normal airway is about 50 centimeterswater average intra-abdominal pressure. It should be understood that thevesicular pressure (bladder pressure) can track intra-abdominal pressureand terms are often similar and used together. “Bladder” orintravesicular pressure is often used to determine and equate withintra-abdominal pressure. The two are sometimes used interchangeably.Stress urinary incontinence and/or bladder physiology can be diagnosed.The system and method as described leads directly to diagnosis. Fiftycentimeters average intra-abdominal pressure over time has been found tocorrespond to an involuntary reflex cough test normal airway. Thus, thestandard deviations or other percentages from that value are used in onenon-limiting example to determine an abnormal airway. In a conductedstudy, the actual value is determined to be about 50.6 centimeters wateras compared to voluntary cough values of about 48 centimeters of water.In an outpatient setting, it is possible to have the nebulizer (anddrug) and only a pad and test SUI. In hospitalized patients or inpatientsettings, this combination is used to measure airway and bladderphysiology and the test combination includes a catheter.

It should be understood that the involuntary cough reflex test (iRCT)gives a higher pressure average than obtained using a voluntary coughtest. The involuntary cough reflex test is thus a valuable medicaldiagnostic tool. In one example, four variables are significant in thisanalysis. These variables include: (1) duration of the event; (2)average intra-abdominal pressure of the event; (3) peak intra-abdominalpressure (max) of the event; and (4) area under the curve. Using thesefour variables, it is possible to process the received data and obtain aspecific diagnosis that could not otherwise be obtained without the useof the involuntary reflex cough test. Individual deficits in a specificvariable or combination of variables are used to characterize specificdiseases and problems and useful as a medical diagnostic tool.

Many modifications and other embodiments of the invention will come tothe mind of one skilled in the art having the benefit of the teachingspresented in the foregoing descriptions and the associated drawings.Therefore, it is understood that the invention is not to be limited tothe specific embodiments disclosed, and that modifications andembodiments are intended to be included within the scope of the appendedclaims.

That which is claimed is:
 1. A nebulizer, comprising: a body comprisingan air channel section and a nebulizer outlet configured to be receivedwithin an oral cavity of a patient; a medication reservoir carried bythe body; an air line having an inlet at one end and extending throughthe air channel section and having an outlet and a venturi nozzle at theoutlet and having a venturi outlet wherein the air line providescontinuous pressure between the input end and outlet end of the air lineand the venturi nozzle is located within a patient's oral cavity whenthe nebulizer is in use; a primary suction line extending from themedication reservoir to the venturi outlet through which medication isdrawn upward and mixed with air passing through the venturi nozzle andnebulized for discharge through the nebulizer outlet; wherein nomedication is drawn upward through the primary suction line fornebulization and discharge through the nebulizer outlet until apredetermined negative inspiratory pressure is created from inhalationby a user to begin air flow through the venturi nozzle and medication isdrawn upward through the primary suction line and nebulized by airflowing through the venturi nozzle to be discharged through thenebulizer outlet.
 2. The nebulizer according to claim 1, wherein the airline, venturi nozzle and discharge outlet are horizontally oriented whenin use.
 3. The nebulizer according to claim 1, wherein nebulizationbegins at a negative inspiratory pressure of from about −3 cmH₂O toabout −52 cmH₂O.
 4. The nebulizer according to claim 1, wherein themedication reservoir is located within a patient's oral cavity when thenebulizer is in use.
 5. The nebulizer according to claim 1, and furthercomprising a diffuser upon which the nebulized medication and airexiting the venturi nozzle impacts to aid nebulization.
 6. The nebulizeraccording to claim 1, and further comprising a secondary suction linethat draws nebulized medication that drops down before discharge throughthe nebulizer outlet.
 7. The nebulizer according to claim 1, and furthercomprising an air flow sensor positioned within the air channel sectionand configured to generate signals indicative of air flow generated by apatient's involuntary cough event occurring at nebulization.
 8. Thenebulizer according to claim 7, and further comprising a processorinterfaced with the air flow sensor and configured to evaluate theinvoluntary cough event.
 9. The nebulizer according to claim 1, whereinsaid nebulizer outlet is configured as an infant pacifier.
 10. Thenebulizer according to claim 9, wherein the nebulizer outlet isconfigured as an infant lollipop pacifier.
 11. The nebulizer accordingto claim 1, and further comprising a nebulizer suction member enclosingthe body and configured as an infant pacifier.
 12. A nebulizer,comprising: a body comprising an air channel section and a nebulizeroutlet configured to be received within an oral cavity of a patient; amedication reservoir carried by the body; an air line having an inlet atone end extending through the air channel section and having an outletand a venturi nozzle at the outlet and having a venturi outlet whereinthe air line provides continuous pressure between the input end andoutput end of the air line and the venturi nozzle is located within apatient's oral cavity when the nebulizer is in use; a primary suctionline extending from the medication reservoir to the venturi outletthrough which medication is drawn upward and mixed with air passingthrough the venturi nozzle and nebulized for discharge through thenebulizer outlet; wherein no medication is drawn upward through theprimary suction line for nebulization and discharge through thenebulizer outlet until a predetermined negative inspiratory pressure iscreated from inhalation by a user to begin air flow through the venturinozzle and medication is drawn upward through the primary suction lineand nebulized by air flowing through the venturi nozzle to be dischargedthrough the nebulizer outlet, and further comprising an air flow sensorpositioned within the air channel section and configured to generatesignals indicative of air flow generated by a patient's involuntarycough event occurring at nebulization; and a processor configured toreceive signals from the air flow sensor and to evaluate the involuntarycough event.
 13. The nebulizer according to claim 12, wherein the airline, venturi nozzle and discharge outlet are horizontally oriented whenin use.
 14. The nebulizer according to claim 12, wherein nebulizationbegins at a negative inspiratory pressure of from about −3 cmH₂O toabout −52 cmH₂O.
 15. The nebulizer according to claim 12, wherein themedication reservoir is located to within a patient's oral cavity whenthe nebulizer is in use.
 16. The nebulizer according to claim 12, andfurther comprising a diffuser upon which the nebulized medication andair exiting the venturi nozzle and impacts to aid nebulization.
 17. Thenebulizer according to claim 12, and further comprising a secondarysuction line that draws nebulized medication that drops down beforedischarge through the nebulizer outlet.
 18. The nebulizer according toclaim 12, wherein said nebulizer outlet is configured as an infantpacifier.
 19. The nebulizer according to claim 18, wherein the nebulizeroutlet is configured as an infant lollipop pacifier.
 20. The nebulizeraccording to claim 12, and further comprising a nebulizer suction memberenclosing the body and configured as an infant pacifier.